Pharmacological investigations of effort-based decision-making in humans: Naltrexone and nicotine

Abstract

Many mental health disorders are characterized by an impaired ability, or willingness, to exert effort to obtain rewards. This impairment is modeled in effort-based decision tasks, and neuropharmacological studies implicate dopamine in this process. However, other transmitter systems such as opioidergic and cholinergic systems have received less attention. Here, in two separate studies we tested the acute effects of naltrexone and nicotine on effort-based decision-making in healthy adults. In Study 1, we compared naltrexone (50mg and 25mg) to placebo, and in Study 2, a pilot study, we compared nicotine (7mg) to placebo. In both studies, participants completed the Effort Expenditure for Rewards Task (EEfRT), which measured effort-based decision-making related to monetary rewards. Although subjects expended greater effort for larger reward magnitude and when there was a higher probability of receiving the reward, neither naltrexone nor nicotine affected willingness to exert effort for monetary rewards. Although the drugs produced significant and typical drug effects on measures of mood and behavior, they did not alter effort-based decision-making. This has implications both for the clinical use of these drugs, as well as for understanding the neuropharmacology of effort-related behavior.

Fig 1. Effect of naltrexone dose (0mg, 25mg, 50mg) on willingness to exert effort in the EEfRT.

Estimated marginal means (EMM) are plotted with standard errors (SE) from mixed-effects model (0mg EMM = 0.19, SE = 0.07; naltrexone (25mg) EMM = 0.16, SE = 0.06; naltrexone (50mg) EMM = 0.15, SE = 0.06). No significant effect of naltrexone on choice of hard task (p = 0.61).

Fig 2. Effect of naltrexone dose (0mg, 25mg, 50mg) on willingness to exert effort across trials.

Estimated marginal means are plotted with standard errors shaded from mixed-effects model. No significant interaction between trial number and naltrexone dose (p = 0.46).

Fig 3. Effect of placebo and nicotine (7mg) on willingness to exert effort on EEfRT.

Estimated marginal means are plotted with standard errors from mixed-effects model (Placebo EMM = 0.56, SE = 0.14; Nicotine EMM = 0.55, SE = 0.15). No significant effect of nicotine dose on choice of hard task (p = 0.86).